Expression of stearoyl coenzyme a desaturase in neuronal cells facilitates pancreatic cancer progression

Pancreatic adenocarcinoma (PDAC) is the most fatal malignant tumor that focuses on men and the elderly (40–85 years) and is aggressive. Its surgical resection rate is only 10-44%, and the rate of local recurrence in the retroperitoneum 1 year after surgery is as high as about 60%. The main reason for local recurrence in the majority of patients is that PDAC is perineural invasion (PNI) and the cancer cells infiltrate and grow along the peripancreatic nerve bundles. The identification of biomarkers associated with the diagnosis of PDAC may help to improve the current difficulty in early diagnosis of pancreatic cancer and guide clinical treatment. We constructed a co-culture model system of Schwann and PDCA cells to determined that Stearoyl Coenzyme A Desaturase (SCD) is a key gene driving the progress of PDAC. Single-cell data files for PDAC were analyzed to compare cellular composition and subpopulation-specific gene expression between control (n = 4) and pancreatic cancer (n = 6). Among 36,277 cells, we obtained a total of 16 subpopulations, including a Neurons subpopulation, by UMAP analysis. Further screening by Mendelian randomization analysis yielded three pairs of key genes corresponding to eQTL-positive outcome causally, the corresponding genes were, in order: the three genes COL18A1, RASSF4, and SCD. Among them, SCD was significantly positively correlated with with the malignant progression of pancreatic cancer, and enriched in signaling pathways such as MTORC1_SIGNALING and P53-PATHWAY. In this study, We further applied CRISPR-Cas9 technology to knock out SCD expression in Schwann cells under co culture system to detect the growth status of PDAC cells. Three genes (COL18A1, RASSF4, SCD) showed significant correlation with PDAC. The identified SCD genes were positively correlated with the development of PDAC. We further demonstrated through experiments that SCD is overexpressed in PDAC tissues, and knocking down SCD in neuronal cells reduces the PDAC cells growth rate and migration ability. In this article, we demonstrated that the upregulation of SCD expression level in neuronal cells is related to the PDAC, and SCD may be a promising candidate for PDAC therapy.